Gliomas are one of the most frequent types of nervous system tumors, making up 32% of the total diagnosed cases. Gliomas often carry a bleak prognosis and thus are among the most devastating diseases. Signs and symptoms depend on several factors (size, rate of growth, localization of the tumor) and are mainly represented by headaches, seizures, neurological deficits, and changes in mental status. The treatment for gliomas generally involves surgical removal, followed by a course of radiation and chemotherapy.
Glioblastoma, a malignant form of glioma, occurs more frequently than other types of primary central nervous system tumors. As for current therapy, temozolomide, an oral methylating chemotherapeutic agent, became the standard of care for newly diagnosed glioblastoma, when used concurrently with external beam radiation followed by adjuvant therapy. Even with the combination of radiotherapy plus temozolomide, median survival was 14.6 months at a median follow-up of 28 months (Stupp et al., New England J. Med., 352:987 (2005)). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone (Id.).
Therefore, in spite of the introduction of temozolomide, further research for the development of new agents active against glioma is warranted. Indeed, there is still an unmet medical need for new potent agents for the treatment of gliomas. The present invention is directed to meeting this and other needs.